The goal of this research is to develop a practical oxidative coupling method for the synthesis of phenol-indole biaryl bonds and to apply this methodology to the synthesis of complex polycyclic peptides. In particular, this research will be directed towards the synthesis of complestatin. Complestatin is the most potent inhibitor of complement activation in humans. Agents that inhibit complement activation are expected to be useful in the treatment of severe allergic reactions and auto-immune diseases. Complestatin is also a novel anti-HIV compound, being the first gp120-CD4 binding inhibitor of microbial origin. Compounds related to complestatin have also shown anti-viral activity. We will develop syntheses of several model peptides as well as a concise and versatile synthesis of complestatin, which can be easily varied to provide complestatin analogs. The synthesis of complestatin will test the limits of current synthetic methodology and provide an impetus for the development of new synthetic methodologies. The synthesis of complestatin analogs will provide insight into its biological mode of action.